The current body of research suggests genetics is more likely to contribute to lung cancer for people who are:
Young (under age 50)FemaleNever-smokers
Scientists have identified certain genetic mutations (alterations in your genetic code) that may increase your risk of lung cancer. But this doesn’t mean that all genetic mutations associated with lung cancer are inherited. You can inherit genetic mutations, or you can acquire these changes at any time during your life due to environmental factors (such as due to smoking or pollution).
Influencing Factors
Family history alone cannot predict if you will or will not get lung cancer. Familial lung cancer is a term that may suggest that a cancer gene is “passed” from parents to children.
Today, researchers regard familial lung cancer as a combination of genetic and environmental factors that increase the risk of lung cancer among family members.
A history of smoking will almost always contribute more substantially to the risk of lung cancer than an inherited predisposition to the disease.
The current evidence suggests that the familial risk of lung cancer is influenced by multiple intersecting factors, including:
HereditySimilar lifestyles (such as smoking and diet)Similar environments (such as indoor and outdoor air pollution)
Secondhand smoke within the home, for example, can increase a person’s risk of lung cancer by 20% to 30%. Similarly, radon exposure in the home—the second leading cause of lung cancer in the United States—may also factor into a person’s familial risk of the disease.
As such, a family history of lung cancer cannot so much predict your likelihood of the disease as highlight the need to adjust modifiable risk factors and keep on heightened alert for any signs or symptoms of lung cancer.
Evidence of Genetic Risks
There are a number of factors suggesting a small hereditary component when it comes to the risk of lung cancer.
Younger Age
In the United States, the average age at which lung cancer is diagnosed is 70. Still, there are people who are diagnosed with lung cancer well before then. In fact, around 1.3% of all lung cancer cases occur in people under 35.
What is interesting about this younger population is that few are smokers, which raises questions about which other factors might contribute to the risk. People who develop lung cancer at a younger age are more likely to have genetic changes associated with the disease.
But a hereditary link to these genetic changes has not been established.
Almost all lung cancers in young adults are adenocarcinomas, a type of cancer closely linked to certain acquired (not inherited) genetic mutations.
Sex
Males and females are about as equally likely to develop lung cancer. Still, there are disparities between the sexes.
Females are not only more likely to develop lung cancer at an earlier age than males, but they are also more likely to have it than male counterparts with the same risk factors.
Genetic or hormonal factors may play a role, possibly by increasing a female’s biological susceptibility to carcinogens (cancer-causing agents) in tobacco smoke.
Several studies have found that females have higher concentrations of an enzyme called CYP1A1, which can temper the body’s response to carcinogens in the lungs and promote the development of cancer. Certain genetic polymorphisms (variations) are linked to the dysregulation of CYP1A1 production and may explain why females are more vulnerable to inhaled carcinogens.
Race
Race and ethnicity are also differentiating factors in the risk of lung cancer. Data from the ongoing Surveillance, Epidemiology, and End Results Program (SEER) notes that African Americans have a far greater risk of lung cancer than any other racial or ethnic group.
The SEER data provided the lung cancer incidence rates for various groups (described in the number of cases per 100,000 people):
Blacks: 76. 1 per 100,000Whites: 69. 7 per 100,000Native Americans: 48. 4 per 100,000Asian/Pacific Islanders: 38. 4 per 100,000Hispanics: 37. 3 per 100,000
Although things like smoking and the environment most certainly contribute to these rates, scientists have also noted that genetic mutations linked to lung cancer can also vary by race.
Future studies may identify how significantly these mutations contribute to the risk among different races and ethnicities, and whether genetic mutations are inherited or acquired.
Gene Mutations
Some types of lung cancer are more strongly linked to specific genetic mutations than others, but they have not been established as inherited. In fact, they are believed to be acquired. These mutations can alter the function and life cycle of a cell, causing it to replicate abnormally and out of control, leading to the onset of cancer.
Scientists have identified certain genetic mutations associated with carcinogenesis (the development of cancer) in the lungs. The vast majority of these mutations are linked to non-small cell lung cancers (NSCLC), especially lung adenocarcinoma, as opposed to small cell lung cancers (SCLC).
EGFR
Mutations of the EGFR gene can alter the production of a protein called epidermal growth factor receptor that helps cells respond appropriately to their environment. There are no fewer than 10 EGFR mutations known to be linked to lung cancer; many more are expected to be identified.
Research suggests that 47% of Asians with NSCLC have an EGFR mutation. Around 21% of people with NSCLC who are of Middle-Eastern or African descent also carry the mutation; the same is true for 12% of patients who are of European descent.
EGFR mutations are also more common in women and non-smokers. While EGFR mutations are mainly linked to lung adenocarcinomas, some can affect squamous cell carcinomas by making them more aggressive.
EGFR mutations can be identified both in the primary (original) tumor and in metastases (secondary tumors that have spread to distant sites). These mutations tend to mutate rapidly and often become resistant to the drugs used to treat them.
KRAS
The KRAS gene is responsible for the production of a signaling protein called K-Ras that instructs cells on how to divide, mature, and function. Dysregulation of this protein can lead to cancer.
Around 15% to 20% of people with lung adenocarcinoma test positive for KRAS mutations. These often occur alongside EGFR mutations.
KRAS mutations are mainly identified in the primary tumor and less commonly in metastatic tumors.
ALK
The anaplastic lymphoma kinase (ALK) gene is responsible for the production of a type of tyrosine kinase protein that instructs cells to divide and grow. The mutation, more accurately referred to as an ALK rearrangement, is linked to NSCLC and is more commonly seen in Asians than any other group.
ALK rearrangement is linked to between 3% and 5% of NSCLC cases (mainly adenocarcinomas) and is more commonly seen in light smokers, non-smokers, and people under 70.
BRCA2
It has been found that people with a BRCA2 gene mutation, one of the mutations associated with breast cancer, are at a higher risk of developing lung cancer as well.
This mutation is found in roughly 2% of people of European ancestry and is inherited in an autosomal dominant pattern (meaning that only one parent has to contribute the mutation to increase the risk of a disease).
Smokers carrying this mutation most often develop squamous cell carcinoma. Squamous cell carcinomas develop in the airways of the lungs, as opposed to adenocarcinomas that develop on the outer edges of the lungs.
Screening and Treatment
Scientists still have much to learn about the genetics of lung cancer. Although there are clear associations between lung cancer and EGFR, KRAS, ALK, and BRAF mutations, these mutations are believed to be acquired and they are only found in the cancer cells, not in other cells of the body. So they can’t be identified before lung cancer develops (but certain inherited mutations such as BRCA1 and BRCA2 can be identified in advance).
At this time, there are no recommendations regarding genetic screening for lung cancer. Research investigations aimed at identifying inherited genes that lead to or predispose to lung cancer are still not yielding definitive information.
These drugs target and kill cancer cells with specific treatable mutations, leaving normal cells largely untouched. Because of this, targeted therapies often cause fewer side effects.
Among the targeted drugs used for NSCLC with an EGFR mutation:
Gilotrif (afatinib) Iressa (gefitinib) Tagrisso (osimertinib) Tarceva (erlotinib) Vizimpro (dacomitinib)
Among the targeted drugs used for NSCLC with an ALK rearrangement:
Alecensa (alectinib)Alunbrig (brigatinib)Lorbrena (lorlatinib)Xalkori (crizotinib)Zykadia (ceritinib)
A Word From Verywell
If you are at high risk for the disease, you may benefit from annual CT screening for lung cancer. Annual screening is currently recommended for people between the ages of 50 and 80 who smoke or have quit in the past 15 years and have at least a 20 pack-year history of smoking.
Depending upon additional risk factors, such as family history or radon exposure, you and your healthcare provider may elect to choose screening outside of these parameters. Doing so may catch lung cancer early while it is still highly treatable.
